Atiprimod is an inhibitor of cancer cell proliferation and angiogenesis

• Published in: Journal of experimental therapeutics & oncology Vol. 4; no. 4; p. 267
• Main Authors: Shailubhai, Kunwar, Dheer, Surendra, Picker, Donald, Kaur, Gurmeet, Sausville, Edward A, Jacob, Gary S
• Format: Journal Article
• Language: English
• Published: United States 01-12-2004
• Subjects: Angiogenesis Inhibitors - pharmacology; Apoptosis; Caspase 3; Caspase 9; Caspases - metabolism; Cations; Cell Line, Tumor; Cell Movement; Cell Proliferation - drug effects; Cells, Cultured; Collagen - pharmacology; Cytokines - metabolism; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Drug; Down-Regulation; Drug Combinations; Endothelium, Vascular - cytology; Enzyme Activation; Fibroblast Growth Factor 2 - metabolism; Humans; Inhibitory Concentration 50; Laminin - pharmacology; Models, Chemical; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms - drug therapy; Neovascularization, Pathologic; Proteoglycans - pharmacology; Spiro Compounds - pharmacology; STAT3 Transcription Factor; Trans-Activators - metabolism; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1359-4117

Atiprimod, a novel compound belonging to the azaspirane class of cationic amphiphilic drugs, exhibits both anti-proliferative and anti-angiogenic activities. Atiprimod inhibited proliferation of all human cancer cell lines included in the National Cancer Institute panel with IC50 values in the low micromolar range. Notably, metastatic cell lines were more sensitive to the compound compared to the non-metastatic cell lines derived from the same tumor tissue types. Atiprimod also induced apoptosis and activated both caspase-9 and caspase-3 in T84 colon carcinoma cells. Hence, the anti-proliferative activity could partly be due to its pro-apoptotic activity. Regarding angiogenesis in vitro, atiprimod inhibited both bFGF and VEGF induced proliferation and migration of human umbilical vein endothelial cells (HUVECs), resulting in disruption of cord formation. In addition, atiprimod also suppressed formation of new blood vessels in a chorioallantoic membrane assay. Previous studies have also shown that atiprimod treatment reduced production of IL-6, VEGF and inhibited activation of Stat3, a constitutively activated protein in majority of human cancers. Together these findings suggest that atiprimod acts on several molecules that are essential for tumor growth, invasion and metastasis.